title: Genotypic/phenotypic correlations in genetic hemochromatosis: evolution of diagnostic criteria.
abstract: OBJECTIVE
  The identification of a candidate gene for hereditary hemochromatosis in 69%-100% of patients with hemochromatosis has resulted in a diagnostic genotypic test (C282Y). The aim of this study was to reassess the phenotypic diagnostic criteria for hemochromatosis in patients homozygous for the C282Y mutation of the HFE gene.
  
  
  METHODS
  Transferrin saturation, ferritin, hepatic iron index, and iron removed by venesection were studied in C282Y++ homozygotes and C282Y-- putative homozygotes.
  
  
  RESULTS
  Patients were homozygous for the C282Y mutation in 122 of 128 cases (95%). In C282Y homozygotes, the results were as follows: hepatic iron index, >1.9 in 91.3%; transferrin saturation, >55% in 90%; serum ferritin, >300 microg/L in 96% of men and >200 microg/L in 97% of women; and iron removed, >5 g in 70% of men and 73% of women. There were four homozygotes for C282Y with no biochemical evidence of iron overload.
  
  
  CONCLUSIONS
  The sensitivity of the phenotypic tests in decreasing order was as follows: serum ferritin, hepatic iron index, transferrin saturation, and iron removed by venesection. Although the genetic test is useful in the diagnostic algorithm, this study has shown both iron-loaded patients without the mutation and homozygous patients without iron overload.
authors.affiliation: Department of Medicine, University of Western Ontario, London, Canada. padams@julian.uwo.ca
authors.forename: P C
authors.initials: PC
authors.lastname: Adams
authors.forename: S
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005293:Ferritins / Q000097:blood; D006680:HLA Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012737:Sex Factors
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron